Collagenase has been implicated in ulceration and perforation of diseased, wounded and alkali-burned corneas. The purpose of this research is to devise chemical means for the control of collagenolytic activity of afflicted eyes by means of active-site-directed modifications of corneal collagenase. The design of such inhibitors is projected from a present knowledge of the structure and properties of collagen and of tissue collagenases using radial diffusion assay. The most potent inhibitors will be tested on corneal tissue explants and finally by direct application to alkali burned corneas of rabbits. The results of these studies may open the way for more effective prevention of secondary corneal loss due to ulceration after eye injury, disease or surgery.